In treating disease it is often useful to treat tissue locally, rather than systemically, with trophic factors, particularly areas of tissue damage as for example in wound healing.
As a further example, transplantation of neural tissue into the mammalian central nervous system (CNS) is becoming an alternative treatment for neurological and neurodegenerative disorders including epilepsy, stroke, Huntington's diseases, head injury, spinal injury, pain, Parkinson's disease, myelin deficiencies, neuromuscular disorders, neurological pain, amyotrophic. lateral sclerosis, Alzheimer's disease, and affective disorders of the brain. Preclinical and clinical data indicate that transplanted cells (the graft) used in cell transplantation protocols for these types of neurodegenerative diseases survive and integrate with the host tissue, and provides functional recovery. (Sanberg et al., 1994).
The primary source for these grafts has been the fetus. For example, fetal ventral mesencephalic tissue has been demonstrated to be a viable graft source in Parkinson's disease. (Lindvall et al., 1990; Bjorklund, 1992). Likewise, fetal striatal tissue has been utilized successfully as graft material in Huntington's disease. (Isacson et al., 1986; Sanberg et al., 1994).
Neurologically dysfunctional animals have been transplanted with non-fetal cells and non-neuronal cells/tissue. For example, chromaffin cells from adult donors have been used in the treatment of Parkinson's disease. The major advantage of this type of transplantation protocol is that the graft source is not a fetal source and, thereby, circumvents the ethical and logistical problems associated with acquiring fetal tissue. Utilizing the chromaffin cell protocol, normalization of behavior is observed. However, the functional recovery of this behavior is temporary and the animals revert to their pre-transplantation status (Bjorklund and Stenevi, 1985; Lindvall et al., 1987). The inability of this type of treatment protocol to maintain normal behavioral activity in animals in the Parkinson's disease model renders clinical application of this protocol as well as other treatment therapies premature.
Administration of growth factors as a means of treating neurological and neurodegenerative diseases has been contemplated in the art. However, delivering these agents to the brain is fraught with great difficulties that have yet to be successfully overcome. Generally, these agents cannot be administered systemically and infusion into the brain is an impractical and imperfect solution. Engineering cells to deliver specific, single trophic factors when implanted in the brain has been suggested, but stable transfection and survival of the cells when implanted in the brain continues to be problematic. Additionally, it is becoming increasingly recognized that multiple trophic factors acting in concert are likely to be necessary for the successful treatment of neurological and neurodegenerative conditions.
Long term maintenance of functional recovery has been observed in a diabetic animal model utilizing a novel transplantation treatment protocol utilizing isolated islet cells and Sertoli cells. It is clear that the efficacy of the treatment is due to the presence of the Sertoli cells, in part, due to their known immunosuppressive secretory factor. (Selawry and Cameron, 1993; Cameron et al., 1990). Sertoli cells are also known to secrete a number of important trophic growth factors.
Accordingly, it would be desirable to utilize Sertoli cells alone as a source for diseases where growth and trophic factor support of damaged tissue is useful. Examples include, wound healing and neurological disorders including neurodegenerative disorders. The Sertoli cells can be used to function as an in situ factory for trophic factors to thereby hasten wound healing and to ameliorate functional and behavioral deficits associated with neurological and neurodegenerative disorders.